Digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children 1–3 years old at a rural facility, Bangladesh: Results from a four arm exploratory study

Background Fibersol-2 has some beneficial effects on human health. We aimed to evaluate the digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children, as well as improvement in stool consistencies in young diarrheal children. Methods Sixty children of either sex, aged 1–3 years having four groups (healthy children/low dose, healthy children/high dose, children with diarrhea/low dose and children with diarrhea/high dose) were enrolled into this exploratory study between 1st August to 23rd October 2017. Two presumptive doses, low (2.5g) and high (5g), twice daily with 50 ml drinking water for seven days were the interventions. Outcomes were to observe the development of possible abdominal symptoms, such as pain, distension, rumbling, and bloating during the intervention and post-intervention periods in healthy and diarrheal children as well as improvement in stool consistencies in diarrheal children. Results Among the diarrheal children, the median (IQR) duration of resolution of diarrhea was 3.9 (2.9, 5.1) days vs. 3.5 (2.0, 8.0) days, p = 0.885; in low dose and high dose groups, respectively. Significant difference was observed in terms of abdominal pain (27% vs. 7%, p = 0.038) and distension (40% vs. 0%, p<0.001) in diarrheal children, compared to healthy children during the pre-intervention period. We also observed significant difference in respect of abdominal distension (23% vs. 0%, p = 0.011), rumbling (27% vs. 0%, p = 0.005) and bloating (43% vs. 3%, p = 0.001) in diarrheal children, compared to healthy children during the intervention period. However, no significant difference was observed in relation to abdominal pain (p = 0.347) and distension (p = 0.165) during the pre-intervention period, compared to the intervention period in diarrheal children. Moreover, no significant difference was observed during the post-intervention period for the diarrheal and healthy children. Conclusion Fibersol-2 was found to be well tolerated in healthy and diarrheal children aged 1–3 years. Trial registration This study was registered as part of a randomized trial at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention were registered.


Introduction
Background 2 Scientific background and explanation of rationale ✔ 3-4 Theories used in designing behavioral interventions

Participants 3
Eligibility criteria for participants, including criteria at different levels in recruitment/sampling plan (e.g., cities, clinics, subjects) ✔ 5 Method of recruitment (e.g., referral, self-selection), including the sampling method if a systematic sampling plan was implemented ✔ 7 Recruitment setting ✔ 6 Settings and locations where the data were collected ✔ 6, 8 Interventions 4 Details of the interventions intended for each study condition and how and when they were actually administered, specifically including: Information on validated instruments such as psychometric and biometric properties ✔ 8-9 Sample Size 7 How sample size was determined and, when applicable, explanation of any interim analyses and stopping rules ✔ 7 Assignment Method 8 Unit of assignment (the unit being assigned to study condition, e.g., individual, group, community) Method used to assign units to study conditions, including details of any restriction (e.g., blocking, stratification, minimization) Inclusion of aspects employed to help minimize potential bias induced due to non-randomization (e.g., matching) Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to study condition assignment; if so, statement regarding how the blinding was accomplished and how it was assessed.
Unit of Analysis 10 Description of the smallest unit that is being analyzed to assess intervention effects (e.g., individual, group, or community) If the unit of analysis differs from the unit of assignment, the analytical method used to account for this (e.g., adjusting the standard error estimates by the design effect or using multilevel analysis) Statistical Methods

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Statistical methods used to compare study groups for primary methods outcome(s), including complex methods of correlated data ✔ 10 Statistical methods used for additional analyses, such as a subgroup analyses and adjusted analysis ✔ 10 Methods for imputing missing data, if used Statistical software or programs used ✔ 9

Results
Participant flow 12 Flow of participants through each stage of the study: enrollment, assignment, allocation, and intervention exposure, follow-up, analysis (a diagram is strongly recommended) o Enrollment: the numbers of participants screened for eligibility, found to be eligible or not eligible, declined to be enrolled, and enrolled in the study Indication of whether the analysis strategy was "intention to treat" or, if not, description of how non-compliers were treated in the analyses Outcomes and estimation 17 For each primary and secondary outcome, a summary of results for each estimation study condition, and the estimated effect size and a confidence interval to indicate the precision

Inclusion of null and negative findings
Inclusion of results from testing pre-specified causal pathways through which the intervention was intended to operate, if any Ancillary analyses 18 Summary of other analyses performed, including subgroup or restricted analyses, indicating which are pre-specified or exploratory Adverse events 19 Summary of all important adverse events or unintended effects in each study condition (including summary measures, effect size estimates, and confidence intervals)

Interpretation 20
Interpretation of the results, taking into account study hypotheses, sources of potential bias, imprecision of measures, multiplicative analyses, and other limitations or weaknesses of the study ✔ 11-13 Discussion of results taking into account the mechanism by which the intervention was intended to work (causal pathways) or alternative mechanisms or explanations ✔ 12 Discussion of the success of and barriers to implementing the intervention, fidelity of implementation Discussion of research, programmatic, or policy implications Generalizability 21 Generalizability (external validity) of the trial findings, taking into account the study population, the characteristics of the intervention, length of follow-up, incentives, compliance rates, specific sites/settings involved in the study, and other contextual issues Overall Evidence

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General interpretation of the results in the context of current evidence and current theory